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D Crimmins

Publications and source records attributed to D Crimmins.

15 recordsLinked to original sources
PubMed2006

Subtypes of oligodendroglioma defined by 1p,19q deletions, differ in the proportion of apoptotic cells but not in replication-licensed non-proliferating cells.

Oligodendrogliomas may be divided into those with deletion of chromosomes 1p and 19q (Del+), and those without (Del-). Del+ tumours show better survival and chemoresponsiveness but the reason for this difference is unknown. We have investigated whether these subgroups differ in (a) apoptotic index, (b) the proportion of cells licensed for DNA replication but not in-cycle, and (c) the relative length of G1-phase. Fluorescence in situ hybridisation with probes to 1p and 19q was used to determine the deletion status of 54 oligodendrogliomas, including WHO grades II and III. The apoptotic index was determined using counts of apoptotic bodies. Replication-licensed non-proliferating cells were determined from the Mcm2 minus Ki67 labelling index, whilst the geminin to Ki67 ratio was used as a measure of the relative length of G1. Del+ oligodendrogliomas showed a higher apoptotic index than Del- tumours (P=0.037); this was not accounted for by differences in tumour grade or in proliferation. There were no differences in the Mcm2-Ki67 index or in the geminin/Ki67 ratio between the subgroups, but grade III tumours showed a higher proportion of licensed non-proliferating cells than grade II tumours (P=0.001). An increased susceptibility to apoptosis in oligodendrogliomas with 1p+/-19q deletion may be important in their improved clinical outcome compared to Del- tumours.

Adult↗
PubMed2005

[Use of telepathology to provide rapid diagnosis of neurosurgical specimens].

To determine whether still digital images of neurosurgical specimens sent by e-mail are an effective and safe way of obtaining an emergency pathological diagnosis, representative images from 48 neurosurgical smear specimens were digitized, compressed and sent by electronic mail to our consultant neuropathologist with relevant clinical and radiological information. The time to select, digitize, compress and send the images for each case was recorded. Comparison was made between diagnosis made from digital images (DI) and historical smear (HS) using the original permanent section (PS) diagnosis as the gold standard. A diagnosis of normal vs. abnormal, neoplastic vs. non-neoplastic, primary vs. secondary and tumor grade was made in each case. The mean time for selection and digitalization of each case was 9.51 minutes. The number of correct pathological diagnosis was 41/48 using DI and 48/48 using HS, giving an accuracy rate of 85.4% and 100% respectively. DI was 100% sensitive in recognizing neoplastic tissue but only 98% specific. Most inaccuracies were in grading and caused by problems with field selection and familiarity with the technique. We conclude that static digital images are reliable and safe method of interpreting tissue during neurosurgical procedures. This corresponds with the findings of previous studies.

Brain Neoplasms↗
PubMed2004

DNA replication licensing and cell cycle kinetics of oligodendroglial tumours.

The convergence point of growth-signalling pathways that control cell proliferation is the initiation of genome replication, the core of which is the assembly of pre-replicative complexes (pre-RCs), resulting in chromatin being 'licensed' for DNA replication in the subsequent S phase. The Mcm2-7 complex is a core constituent of the pre-RC, whose recruitment to replication origins is dependent on the Cdt1 loading factor. Geminin is a potent inhibitor of the initiation of DNA replication by preventing Mcm2-7 assembly at origins via its interaction with Cdt1, ensuring genomic integrity through suppression of re-initiation events in S phase. Here we investigate the regulation of Ki67, Mcm2, p21, caspase 3 and Geminin in a series of 55 oligodendrogliomas to provide an integrated picture of how cellular proliferation and programmed cell death are dysregulated in these tumours. Geminin does not behave as an inhibitor of cell proliferation, its labelling index rising with increasing growth fraction as defined by Ki67 or Mcm2 expression. Geminin is expressed in a higher proportion of cells in higher grade tumours (P<0.001) and shows a strong correlation to proliferation and replication licensing (P<0.01), but not apoptosis. Increasing tumour anaplasia is not associated with loss of Geminin. Importantly, the G1 phase of the proliferative cell cycle, as assessed by the Geminin/Ki67 ratio, shortens with increasing anaplasia, providing new potential algorithms for prognostic assessment. Origin licensing proteins thus provide powerful novel tools for assessment of tumour cell cycle kinetics in routinely processed surgical biopsy material.

Adult↗
PubMed1999

Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM.

Mutations in the brain specific P/Q type Ca2+ channel alpha1 subunit gene, CACNA1A, have been identified in three clinically distinct disorders, viz. episodic ataxia type 2 (EA-2), familial hemiplegic migraine (FHM) and spinocerebellar ataxia 6 (SCA6). For individuals with EA-2, the mutations described thus far are presumed to result in a truncated protein product. Several different missense mutations have been identified in patients with FHM. At least two of these mutations have been identified on two different chromosome 19p13 haplotypes and thus represent recurrent mutations. In the present study, we have screened several individuals for mutations in all 47 exons in the CACNA1A gene by single-strand conformation analysis. We have characterised a novel missense mutation, G5260A, in exon 32 in a family segregating for EA-2. The consequence of this mutation is an amino acid substitution at a highly conserved position within the CACNA1A gene. This represents the first point mutation not resulting in a proposed truncated protein. Furthermore, this mutation has been detected in a family member with mild clinical signs including only migraine. Additionally, a second previously identified recurrent muta tion, C2272T, in exon 16 has been discovered in a patient with FHM.

Amino Acid Sequence↗
PubMed1999

Development, characterization, and use of monoclonal antibodies made to antigens expressed on the surface of fetal nucleated red blood cells.

BACKGROUND: Current methods for obtaining fetal cells for prenatal diagnosis are invasive and carry a small (0.5-1.0%) but definite risk of miscarriage. An attractive alternative would be isolation of fetal cells from peripheral maternal blood using antibodies with high specificity and avidity. METHODS: To generate antibodies, we purified nucleated red blood cells (NRBCs) from fetal livers and used them as the immunogen to generate monoclonal antibodies (mAbs) directed against surface antigens. RESULTS: The four antibodies recognized at least two conformationally sensitive epitopes of the transferrin receptor. Isolation of NRBCs from 252 maternal blood samples using these antibodies in magnetic activated cell sorting after an initial density gradient centrifugation yielded 0-419 NRBCs per 25 mL of maternal blood. One antibody, 2B7.4, not only isolated the highest number of NRBCs (>10 in 90% of the samples) but also isolated these NRBCs in 78 consecutive maternal samples. CONCLUSION: Antibody 2B7.4 shows promise for the isolation of NRBCs from maternal blood and should allow studies concerning the source of these cells, fetal vs maternal, and the factors controlling their prevalence.

Animals↗
PubMed1994

Hospital practices influence the pattern of infective endocarditis.

OBJECTIVE: To identify factors contributing to infective endocarditis at a major teaching hospital. METHODS: Retrospective review of clinical records of patients diagnosed with endocarditis by standard case definitions with respect to causative organisms, clinical features and outcome. RESULTS: One hundred and ninety-three episodes of endocarditis seen between 1979 and 1992 at Westmead Hospital, Sydney, were reviewed. In the 174 cases where the causative organism was isolated, 75 (43%) were Staphylococcus aureus and 50 (29%) were viridans streptococci. Nosocomial acquisition and/or inter-hospital transfer accounted for 83 episodes; 48 (58%) S. aureus (P < 0.001) and nine (11%) viridans streptococci (P < 0.001). In cases from the local community, viridans streptococci were more common than S. aureus (37% versus 25%); these included 18 episodes (14 S. aureus) in intravenous drug users. CONCLUSION: We conclude that, compared with community-acquired infections, the aetiology of endocarditis in a large teaching hospital is influenced strongly by the prevalence of nosocomial endocarditis and the need for interhospital transfer of complicated cases.

Community-Acquired Infections↗
PubMed1994

Heterogeneity in the phenotypic expression of the mutation in the mitochondrial tRNA(Leu) (UUR) gene generally associated with the MELAS subset of mitochondrial encephalomyopathies.

BACKGROUND: Point mutations in the mitochondrial (mt) genome underlie a number of neurological disorders. Some are well defined including the myoclonus epilepsy ragged red fibre syndrome (MERRF) and the mitochondrial encephalopathy lactic acidosis stroke like episode syndrome (MELAS). However, other clinical phenotypes are less distinctive and mitochondrial studies are often included in the workup in complex neurological syndromes of uncertain aetiology. AIMS: We investigated 27 consecutive patients with varied clinical phenotypes referred to our laboratory for mtDNA studies to determine the incidence of recognised point mutations in a patient group with a range of phenotypes including many where mt disease was possible but did not fall into a classical syndrome. METHODS: The recognised point mutations were detected by amplification of the appropriate DNA fragment by PCR followed by restriction-endonuclease digestion of the normal and mutant species. RESULTS: The A-G base substitution mutation at nucleotide (nt)3243 in the tRNA(Leu) gene of mtDNA which is present in the majority of cases of MELAS syndrome, was detected in four cases, only one of whom had typical MELAS symptoms. Their clinical manifestations ranged from mild deafness to a mixture of chronic progressive external ophthalmoplegia symptoms (CPEO) and stroke like episodes. The nt3243 mutation was also identified in one of seven mtDNA deletion negative CPEO cases. CONCLUSIONS: The presentation of the mtDNA mutation at nt3243 appears therefore to be quite variable with some mild phenotypes as well as severe phenotypes observed. In general, the chance of finding a mitochondrial point mutation in a patient with an atypical clinical phenotype is small.

Adult↗
PubMed1993

Mitochondrial encephalomyopathy: variable clinical expression within a single kindred.

The clinical manifestations of mitochondrial encephalomyopathy are described in four generations of a single kindred. The age of onset of major neurological disturbance varied from 3-70 years. In some patients, deafness was the only manifestation; in others, recurrent bouts of status epilepticus associated with focal neurological deficits and headache, caused severe disability or death. Examples of all three adult forms of mitochondrial encephalomyopathy: MELAS, MERFF and Kearns Sayre syndrome, were represented within the kindred. Associated features included deafness, short stature, non-insulin-dependent diabetes mellitus, migraine, peptic ulceration and severe constipation. The nt 3243 A-G MELAS mutation was detected in two members of the kindred. This study highlights the diversity of clinical expression of a mitochondrial mutation within a single kindred.

Adolescent↗
PubMed1990

Neurocysticercosis: an under-recognized cause of neurological problems.

Neurocysticercosis is an uncommon, and under-recognized condition in Australia. Changes in immigration patterns may lead to a rising prevalence in this country. Epilepsy is the most common presentation, but it has many other variable forms of neurological manifestations. Eight cases are described, all in immigrants from Eastern Europe, Asia or Central America; the disease was presumably acquired before arrival in Australia. Six patients had symptoms for two to 30 years before the diagnosis was made and, in some cases, the first neurological manifestations appeared decades after initial infection. In patients with active disease a successful outcome followed therapy with praziquantel and corticosteroids. We advise that all patients requiring treatment be admitted to hospital for corticosteroid and anticonvulsant therapy to minimize the clinical deterioration which may result from therapeutic destruction of larvae.

Adolescent↗
PubMed1990

Lead intoxication in an anuric patient: management by intraperitoneal EDTA.

Treatment of lead intoxication with intravenous ethylene-diamine-tetra-acetic acid (EDTA) depends on the urinary excretion of chelated lead. This route of excretion was absent in a 48-year-old patient with childhood lead exposure and end stage renal failure who developed encephalopathy and a rapidly progressive neuropathy thought to be due to acute lead intoxication. Diagnosis was confirmed by lead chelation with EDTA and neurophysiological studies. EDTA was added by the patient to her chronic ambulatory peritoneal dialysis (CAPD) fluid each week and chelated lead excreted in the dialysate. Intraperitoneal administration of EDTA was 70% as efficient in removing lead as intravenous administration. Four months of home chelation therapy was associated with resolution of the encephalopathy but no improvement in the peripheral neuropathy.

Anuria↗
PubMed1990

A comparison of two methods of eliciting the ankle jerk.

Two methods of eliciting the ankle jerk have been compared. One, the traditional method, involved tapping the Achilles tendon (the tendon tap); the other (the plantar tap) involved tapping the sole of the foot. The study was done on 110 inpatients in the medical wards of a teaching hospital. The results showed an 89% agreement between the two methods. The extent of agreement was unrelated to the level of experience of the examiner. Forty three per cent of patients favoured the plantar tap method; 14% the tendon tap. The plantar tap method of eliciting the ankle jerk is an acceptable alternative to the traditional method.

Adult↗